Neural activity shaping in visual prostheses with deep learning.

OBJECTIVE: The visual perception provided by retinal prostheses is limited by the overlapping current spread of adjacent electrodes. This reduces the spatial resolution attainable with unipolar stimulation. Conversely, simultaneous multipolar stimulation guided by the measured neural responses - Neural Activity Shaping (NAS) - can attenuate excessive spread of excitation allowing for more precise control over the pattern of neural activation. However, predicting the results of a multipolar stimulus pattern is a challenging task. Previous attempts focused on analytical solutions based on an assumed linear nonlinear model of retinal response; an Analytical Model Inversion (AMI) approach. Here, we propose a model-free solution for NAS, using Artificial Neural Networks (ANNs) that could be trained with data acquired from the implant. APPROACH: Our method consists of two ANNs trained sequentially. The Measurement Predictor Network (MPN) is trained on data from the implant and is used to predict how the retina responds to multipolar stimulation. The Stimulus Generator Network (STG) is trained on a large dataset of natural images and uses the trained MPN to determine efficient multipolar stimulus patterns by learning its inverse model. We validate our method in silico using a realistic model of retinal response to multipolar stimulation. Main Results: We show that our ANN-based NAS approach produces sharper retinal activations than the conventional unipolar stimulation strategy. As a theoretical bench-mark of optimal NAS results, we implemented AMI stimulation by inverting the model used to simulate the retina. Our ANN strategy produced equivalent results to AMI, while not being restricted to any specific type of retina model and being three orders of magnitude more computationally efficient. SIGNIFICANCE: Our novel protocol provides a method for efficient and personalized retinal stimulation, which may improve the visual experience and quality of life of retinal prosthesis users. .

Quantifying visual acuity for pre-clinical testing of visual prostheses.

Objective.Visual prostheses currently restore only limited vision. More research and pre-clinical work are required to improve the devices and stimulation strategies that are used to induce neural activity that results in visual perception. Evaluation of candidate strategies and devices requires an objective way to convert measured and modelled patterns of neural activity into a quantitative measure of visual acuity.Approach.This study presents an approach that compares evoked patterns of neural activation with target and reference patterns. A d-prime measure of discriminability determines whether the evoked neural activation pattern is sufficient to discriminate between the target and reference patterns and thus provides a quantified level of visual perception in the clinical Snellen and MAR scales. The magnitude of the resulting value was demonstrated using scaled standardized 'C' and 'E' optotypes.Main results.The approach was used to assess the visual acuity provided by two alternative stimulation strategies applied to simulated retinal implants with different electrode pitch configurations and differently sized spreads of neural activity. It was found that when there is substantial overlap in neural activity generated by different electrodes, an estimate of acuity based only upon electrode pitch is incorrect; our proposed method gives an accurate result in both circumstances.Significance.Quantification of visual acuity using this approach in pre-clinical development will allow for more rapid and accurate prototyping of improved devices and neural stimulation strategies.

Neural activity shaping utilizing a partitioned target pattern.

Electrical stimulation of neural tissue is used in both clinical and experimental devices to evoke a desired spatiotemporal pattern of neural activity. These devices induce a local field that drives neural activation, referred to as an activating function or generator signal. In visual prostheses, the spread of generator signal from each electrode within the neural tissue results in a spread of visual perception, referred to as a phosphene.Objective.In cases where neighbouring phosphenes overlap, it is desirable to use current steering or neural activity shaping strategies to manipulate the generator signal between the electrodes to provide greater control over the total pattern of neural activity. Applying opposite generator signal polarities in neighbouring regions of the retina forces the generator signal to pass through zero at an intermediate point, thus inducing low neural activity that may be perceived as a high-contrast line. This approach provides a form of high contrast visual perception, but it requires partitioning of the target pattern into those regions that use positive or negative generator signals. This discrete optimization is an NP-hard problem that is subject to being trapped in detrimental local minima.Approach.This investigation proposes a new partitioning method using image segmentation to determine the most beneficial positive and negative generator signal regions. Utilizing a database of 1000 natural images, the method is compared to alternative approaches based upon the mean squared error of the outcome.Main results.Under nominal conditions and with a set computation limit, partitioning provided improvement for 32% of these images. This percentage increased to 89% when utilizing image pre-processing to emphasize perceptual features of the images. The percentage of images that were dealt with most effectively with image segmentation increased as lower computation limits were imposed on the algorithms.Significance.These results provide a new method to increase the resolution of neural stimulating arrays and thus improve the experience of visual prosthesis users.

Global activity shaping strategies for a retinal implant.

OBJECTIVE: Retinal prostheses provide visual perception via electrical stimulation of the retina using an implanted array of electrodes. The retinal activation resulting from each electrode is not point-like; instead each electrode introduces a spread of retinal activation that may overlap with activations from other electrodes. With most conventional stimulation strategies this overlap leads to image blur. Here we propose a 'shaping' algorithm that uses multiple electrodes to manipulate the current between electrodes in a desired way. APPROACH: We assume a forward model for the conversion of electrode strengths to retinal activation. Three alternative global shaping algorithms are developed by calculating reverse models under different assumptions: linear inversion using singular value decomposition to produce the pseudoinverse, a linearly constrained quadratic program, and a binary quadratic program to partition the target pattern. The algorithms were assessed using both the mean squared error between the resulting images and desired images, as well as their adherence to the maximum allowed electrode currents. MAIN RESULTS: Under wide activation spreads the linear inversion algorithm gave improved solutions but faced two limitations: under low-noise conditions the electrode amplitudes exceeded their set limit; the set of solutions did not include the possibility of using negative local currents to induce retinal activation. The linearly constrained quadratic program and binary quadratic program respectively addressed these problems, but required much greater computation time. SIGNIFICANCE: This provides a framework for improving the resolution of future retinal implants, especially those with high density electrode arrays.

Compensation for Traveling Wave Delay Through Selection of Dendritic Delays Using Spike-Timing-Dependent Plasticity in a Model of the Auditory Brainstem.

Asynchrony among synaptic inputs may prevent a neuron from responding to behaviorally relevant sensory stimuli. For example, "octopus cells" are monaural neurons in the auditory brainstem of mammals that receive input from auditory nerve fibers (ANFs) representing a broad band of sound frequencies. Octopus cells are known to respond with finely timed action potentials at the onset of sounds despite the fact that due to the traveling wave delay in the cochlea, synaptic input from the auditory nerve is temporally diffuse. This paper provides a proof of principle that the octopus cells' dendritic delay may provide compensation for this input asynchrony, and that synaptic weights may be adjusted by a spike-timing dependent plasticity (STDP) learning rule. This paper used a leaky integrate and fire model of an octopus cell modified to include a "rate threshold," a property that is known to create the appropriate onset response in octopus cells. Repeated audio click stimuli were passed to a realistic auditory nerve model which provided the synaptic input to the octopus cell model. A genetic algorithm was used to find the parameters of the STDP learning rule that reproduced the microscopically observed synaptic connectivity. With these selected parameter values it was shown that the STDP learning rule was capable of adjusting the values of a large number of input synaptic weights, creating a configuration that compensated the traveling wave delay of the cochlea.

Broadband onset inhibition can suppress spectral splatter in the auditory brainstem.

In vivo intracellular responses to auditory stimuli revealed that, in a particular population of cells of the ventral nucleus of the lateral lemniscus (VNLL) of rats, fast inhibition occurred before the first action potential. These experimental data were used to constrain a leaky integrate-and-fire (LIF) model of the neurons in this circuit. The post-synaptic potentials of the VNLL cell population were characterized using a method of triggered averaging. Analysis suggested that these inhibited VNLL cells produce action potentials in response to a particular magnitude of the rate of change of their membrane potential. The LIF model was modified to incorporate the VNLL cells' distinctive action potential production mechanism. The model was used to explore the response of the population of VNLL cells to simple speech-like sounds. These sounds consisted of a simple tone modulated by a saw tooth with exponential decays, similar to glottal pulses that are the repeated impulses seen in vocalizations. It was found that the harmonic component of the sound was enhanced in the VNLL cell population when compared to a population of auditory nerve fibers. This was because the broadband onset noise, also termed spectral splatter, was suppressed by the fast onset inhibition. This mechanism has the potential to greatly improve the clarity of the representation of the harmonic content of certain kinds of natural sounds.

An investigation of dendritic delay in octopus cells of the mammalian cochlear nucleus.

Octopus cells, located in the mammalian auditory brainstem, receive their excitatory synaptic input exclusively from auditory nerve fibers (ANFs). They respond with accurately timed spikes but are broadly tuned for sound frequency. Since the representation of information in the auditory nerve is well understood, it is possible to pose a number of questions about the relationship between the intrinsic electrophysiology, dendritic morphology, synaptic connectivity, and the ultimate functional role of octopus cells in the brainstem. This study employed a multi-compartmental Hodgkin-Huxley model to determine whether dendritic delay in octopus cells improves synaptic input coincidence detection in octopus cells by compensating for the cochlear traveling wave delay. The propagation time of post-synaptic potentials from synapse to soma was investigated. We found that the total dendritic delay was approximately 0.275 ms. It was observed that low-threshold potassium channels in the dendrites reduce the amplitude dependence of the dendritic delay of post-synaptic potentials. As our hypothesis predicted, the model was most sensitive to acoustic onset events, such as the glottal pulses in speech when the synaptic inputs were arranged such that the model's dendritic delay compensated for the cochlear traveling wave delay across the ANFs. The range of sound frequency input from ANFs was also investigated. The results suggested that input to octopus cells is dominated by high frequency ANFs.

Direct puncture capsulorhexis.

I describe a simple technique for performing capsulorhexis without viscoelastic material or expensive instruments. A slightly barbed, bent, 30-gauge needle is used to directly puncture clear cornea and create a capsulorhexis without the need for a groove or stab incision. Hydrodissection is carried out with the attached 1 cc syringe (tuberculin) filled with a balanced salt solution. Hydrodissection, hydrodelineation, and mobilization of the nucleus can be carried out before the eye is entered with a blade. With direct puncture, the technique is immune to the effects of high intraocular pressure and a shallow anterior chamber. The Technique is ideally suited for bimanual microincision phacoemulsification.